The emergence of drug-resistant bacteria poses a significant threat to people's lives and health as bacterial infections continue to persist. Currently, antibiotic therapy remains the primary approach for tackling bacterial infections. However, the escalating rates of drug resistance coupled with the lag in the development of novel drugs have led to diminishing effectiveness of conventional treatments. Therefore, the development of nonantibiotic-dependent therapeutic strategies has become imperative to impede the rise of bacterial resistance. The emergence of chemodynamic therapy (CDT) has opened up a new possibility due to the CDT can convert HO into •OH via Fenton/Fenton-like reaction for drug-resistant bacterial treatment. However, the efficacy of CDT is limited by a variety of practical factors. To overcome this limitation, the sterilization efficiency of CDT can be enhanced by introducing the therapeutics with inherent antimicrobial capability. In addition, researchers have explored CDT-based combined therapies to augment its antimicrobial effects and mitigate its potential toxic side effects toward normal tissues. This review examines the research progress of CDT in the antimicrobial field, explores various strategies to enhance CDT efficacy and presents the synergistic effects of CDT in combination with other modalities. And last, the current challenges faced by CDT and the future research directions are discussed.